Search results for: extensively drug resistant (XDR)-TB
24 Assessing Image Quality in Mobile Radiography: A Phantom-Based Evaluation of a New Lightweight Mobile X-Ray Equipment
Authors: May Bazzi, Shafik Tokmaj, Younes Saberi, Mats Geijer, Tony Jurkiewicz, Patrik Sund, Anna Bjällmark
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Mobile radiography, employing portable X-ray equipment, has become a routine procedure within hospital settings, with chest X-rays in intensive care units standing out as the most prevalent mobile X-ray examinations. This approach is not limited to hospitals alone, as it extends its benefits to imaging patients in various settings, particularly those too frail to be transported, such as elderly care residents in nursing homes. Moreover, the utility of mobile X-ray isn't confined solely to traditional healthcare recipients; it has proven to be a valuable resource for vulnerable populations, including the homeless, drug users, asylum seekers, and patients with multiple co-morbidities. Mobile X-rays reduce patient stress, minimize costly hospitalizations, and offer cost-effective imaging. While studies confirm its reliability, further research is needed, especially regarding image quality. Recent advancements in lightweight equipment with enhanced battery and detector technology provide the potential for nearly handheld radiography. The main aim of this study was to evaluate a new lightweight mobile X-ray system with two different detectors and compare the image quality with a modern stationary system. Methods: A total of 74 images of the chest (chest anterior-posterior (AP) views and chest lateral views) and pelvic/hip region (AP pelvis views, hip AP views, and hip cross-table lateral views) were acquired on a whole-body phantom (Kyotokagaku, Japan), utilizing varying image parameters. These images were obtained using a stationary system - 18 images (Mediel, Sweden), a mobile X-ray system with a second-generation detector - 28 images (FDR D-EVO II; Fujifilm, Japan) and a mobile X-ray system with a third-generation detector - 28 images (FDR D-EVO III; Fujifilm, Japan). Image quality was assessed by visual grading analysis (VGA), which is a method to measure image quality by assessing the visibility and accurate reproduction of anatomical structures within the images. A total of 33 image criteria were used in the analysis. A panel of two experienced radiologists, two experienced radiographers, and two final-term radiographer students evaluated the image quality on a 5-grade ordinal scale using the software Viewdex 3.0 (Viewer for Digital Evaluation of X-ray images, Sweden). Data were analyzed using visual grading characteristics analysis. The dose was measured by the dose-area product (DAP) reported by the respective systems. Results: The mobile X-ray equipment (both detectors) showed significantly better image quality than the stationary equipment for the pelvis, hip AP and hip cross-table lateral images with AUCVGA-values ranging from 0.64-0.92, while chest images showed mixed results. The number of images rated as having sufficient quality for diagnostic use was significantly higher for mobile X-ray generation 2 and 3 compared with the stationary X-ray system. The DAP values were higher for the stationary compared to the mobile system. Conclusions: The new lightweight radiographic equipment had an image quality at least as good as a fixed system at a lower radiation dose. Future studies should focus on clinical images and consider radiographers' viewpoints for a comprehensive assessment.Keywords: mobile x-ray, visual grading analysis, radiographer, radiation dose
Procedia PDF Downloads 5423 Photobleaching Kinetics and Epithelial Distribution of Hexylaminoleuilinate Induced PpIX in Rat Bladder Cancer
Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin
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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy
Procedia PDF Downloads 40022 Effect of Velocity-Slip in Nanoscale Electroosmotic Flows: Molecular and Continuum Transport Perspectives
Authors: Alper T. Celebi, Ali Beskok
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Electroosmotic (EO) slip flows in nanochannels are investigated using non-equilibrium molecular dynamics (MD) simulations, and the results are compared with analytical solution of Poisson-Boltzmann and Stokes (PB-S) equations with slip contribution. The ultimate objective of this study is to show that well-known continuum flow model can accurately predict the EO velocity profiles in nanochannels using the slip lengths and apparent viscosities obtained from force-driven flow simulations performed at various liquid-wall interaction strengths. EO flow of aqueous NaCl solution in silicon nanochannels are simulated under realistic electrochemical conditions within the validity region of Poisson-Boltzmann theory. A physical surface charge density is determined for nanochannels based on dissociations of silanol functional groups on channel surfaces at known salt concentration, temperature and local pH. First, we present results of density profiles and ion distributions by equilibrium MD simulations, ensuring that the desired thermodynamic state and ionic conditions are satisfied. Next, force-driven nanochannel flow simulations are performed to predict the apparent viscosity of ionic solution between charged surfaces and slip lengths. Parabolic velocity profiles obtained from force-driven flow simulations are fitted to a second-order polynomial equation, where viscosity and slip lengths are quantified by comparing the coefficients of the fitted equation with continuum flow model. Presence of charged surface increases the viscosity of ionic solution while the velocity-slip at wall decreases. Afterwards, EO flow simulations are carried out under uniform electric field for different liquid-wall interaction strengths. Velocity profiles present finite slips near walls, followed with a conventional viscous flow profile in the electrical double layer that reaches a bulk flow region in the center of the channel. The EO flow enhances with increased slip at the walls, which depends on wall-liquid interaction strength and the surface charge. MD velocity profiles are compared with the predictions from analytical solutions of the slip modified PB-S equation, where the slip length and apparent viscosity values are obtained from force-driven flow simulations in charged silicon nano-channels. Our MD results show good agreements with the analytical solutions at various slip conditions, verifying the validity of PB-S equation in nanochannels as small as 3.5 nm. In addition, the continuum model normalizes slip length with the Debye length instead of the channel height, which implies that enhancement in EO flows is independent of the channel height. Further MD simulations performed at different channel heights also shows that the flow enhancement due to slip is independent of the channel height. This is important because slip enhanced EO flow is observable even in micro-channels experiments by using a hydrophobic channel with large slip and high conductivity solutions with small Debye length. The present study provides an advanced understanding of EO flows in nanochannels. Correct characterization of nanoscale EO slip flow is crucial to discover the extent of well-known continuum models, which is required for various applications spanning from ion separation to drug delivery and bio-fluidic analysis.Keywords: electroosmotic flow, molecular dynamics, slip length, velocity-slip
Procedia PDF Downloads 15221 Brain-Derived Neurotrophic Factor and It's Precursor ProBDNF Serum Levels in Adolescents with Mood Disorders: 2-Year Follow-Up Study
Authors: M. Skibinska, A. Rajewska-Rager, M. Dmitrzak-Weglarz, N. Lepczynska, P. Sibilski, P. Kapelski, J. Pawlak, J. Twarowska-Hauser
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Introduction: Neurotrophic factors have been implicated in neuropsychiatric disorders. Brain-Derived Neurotrophic Factor (BDNF) influences neuron differentiation in development as well as synaptic plasticity and neuron survival in adulthood. BDNF is widely studied in mood disorders and has been proposed as a biomarker for depression. BDNF is synthesized as precursor protein – proBDNF. Both forms are biologically active and exert opposite effects on neurons. Aim: The aim of the study was to examine the serum levels of BDNF and proBDNF in unipolar and bipolar young patients below 24 years old during hypo/manic, depressive episodes and in remission compared to healthy control group. Methods: In a prospective 2 years follow-up study, we investigated alterations in levels of BDNF and proBDNF in 79 patients (23 males, mean age 19.08, SD 3.3 and 56 females, mean age 18.39, SD 3.28) diagnosed with mood disorders: unipolar and bipolar disorder compared with 35 healthy control subjects (7 males, mean age 20.43, SD 4.23 and 28 females, mean age 21.25, SD 2.11). Clinical characteristics including mood, comorbidity, family history, and treatment, were evaluated during control visits and clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Serum BDNF and proBDNF concentrations were determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Serum BDNF and proBDNF levels were analysed with covariates: sex, age, age > 18 and < 18 years old, family history of affective disorders, drug-free vs. medicated status. Normality of the data was tested using Shapiro-Wilk test. Levene’s test was used to calculate homogeneity of variance. Non-parametric Tests: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient were applied in analyses The statistical significance level was set at p < 0.05. Results: BDNF and proBDNF serum levels did not differ between patients at baseline and controls as well as comparing patients in acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6). Comparing BDNF and proBDNF levels between patients in euthymia and control group no differences have been found. Increased BDNF level in women compared to men at baseline (p=0.01) have been observed. BDNF level at baseline was negatively correlated with depression and mania occurence at 24 month (p=0.04). BDNF level at 12 month was negatively correlated with depression and mania occurence at 12 month (p=0.01). Correlation of BDNF level with sex have been detected (p=0.01). proBDNF levels at month 3, 6 and 12 negatively correlated with disease status (p=0.02, p=0.008, p=0.009, respectively). No other correlations of BDNF and proBDNF levels with clinical and demographical variables have been detected. Discussion: Our results did not show any differences in BDNF and proBDNF levels between depression, mania, euthymia, and controls. Imbalance in BDNF/proBDNF signalling may be involved in pathogenesis of mood disorders. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.Keywords: bipolar disorder, Brain-Derived Neurotrophic Factor (BDNF), proBDNF, unipolar depression
Procedia PDF Downloads 23820 Study of the Biological Activity of a Ganglioside-Containing Drug (Cronassil) in an Experimental Model of Multiple Sclerosis
Authors: Hasmik V. Zanginyan, Gayane S. Ghazaryan, Laura M. Hovsepyan
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Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system that is induced in laboratory animals by developing an immune response against myelin epitopes. The typical clinical course is ascending palsy, which correlates with inflammation and tissue damage in the thoracolumbar spinal cord, although the optic nerves and brain (especially the subpial white matter and brainstem) are also often affected. With multiple sclerosis, there is a violation of lipid metabolism in myelin. When membrane lipids (glycosphingolipids, phospholipids) are disturbed, metabolites not only play a structural role in membranes but are also sources of secondary mediators that transmit multiple cellular signals. The purpose of this study was to investigate the effect of ganglioside as a therapeutic agent in experimental multiple sclerosis. The biological activity of a ganglioside-containing medicinal preparation (Cronassial) was evaluated in an experimental model of multiple sclerosis in laboratory animals. An experimental model of multiple sclerosis in rats was obtained by immunization with myelin basic protein (MBP), as well as homogenization of the spinal cord or brain. EAE was induced by administering a mixture of an encephalitogenic mixture (EGM) with Complete Freund’s Adjuvant. Mitochondrial fraction was isolated in a medium containing 0,25 M saccharose and 0, 01 M tris buffer, pH - 7,4, by a method of differential centrifugation on a K-24 centrifuge. Glutathione peroxidase activity was assessed by reduction reactions of hydrogen peroxide (H₂O₂) and lipid hydroperoxides (ROOH) in the presence of GSH. LPO activity was assessed by the amount of malondialdehyde (MDA) in the total homogenate and mitochondrial fraction of the spinal cord and brain of control and experimental autoimmune encephalomyelitis rats. MDA was assessed by a reaction with Thiobarbituric acid. For statistical data analysis on PNP, SPSS (Statistical Package for Social Science) package was used. The nature of the distribution of the obtained data was determined by the Kolmogorov-Smirnov criterion. The comparative analysis was performed using a nonparametric Mann-Whitney test. The differences were statistically significant when р ≤ 0,05 or р ≤ 0,01. Correlational analysis was conducted using a nonparametric Spearman test. In the work, refrigeratory centrifuge, spectrophotometer LKB Biochrom ULTROSPECII (Sweden), pH-meter PL-600 mrc (Israel), guanosine, and ATP (Sigma). The study of the process of lipid peroxidation in the total homogenate of the brain and spinal cord in experimental animals revealed an increase in the content of malonic dialdehyde. When applied, Cronassial observed normalization of lipid peroxidation processes. Reactive oxygen species, causing lipid peroxidation processes, can be toxic both for neurons and for oligodendrocytes that form myelin, causing a violation of their lipid composition. The high content of lipids in the brain and the uniqueness of their structure determines the nature of the development of LPO processes. The lipid layer of cellular and intracellular membranes performs two main functions -barrier and matrix (structural). Damage to the barrier leads to dysregulation of intracellular processes and severe disorders of cellular functions.Keywords: experimental autoimmune encephalomyelitis, multiple sclerosis, neuroinflammation, therapy
Procedia PDF Downloads 8519 Utilization of Informatics to Transform Clinical Data into a Simplified Reporting System to Examine the Analgesic Prescribing Practices of a Single Urban Hospital’s Emergency Department
Authors: Rubaiat S. Ahmed, Jemer Garrido, Sergey M. Motov
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Clinical informatics (CI) enables the transformation of data into a systematic organization that improves the quality of care and the generation of positive health outcomes.Innovative technology through informatics that compiles accurate data on analgesic utilization in the emergency department can enhance pain management in this important clinical setting. We aim to establish a simplified reporting system through CI to examine and assess the analgesic prescribing practices in the EDthrough executing a U.S. federal grant project on opioid reduction initiatives. Queried data points of interest from a level-one trauma ED’s electronic medical records were used to create data sets and develop informational/visual reporting dashboards (on Microsoft Excel and Google Sheets) concerning analgesic usage across several pre-defined parameters and performance metrics using CI. The data was then qualitatively analyzed to evaluate ED analgesic prescribing trends by departmental clinicians and leadership. During a 12-month reporting period (Dec. 1, 2020 – Nov. 30, 2021) for the ongoing project, about 41% of all ED patient visits (N = 91,747) were for pain conditions, of which 81.6% received analgesics in the ED and at discharge (D/C). Of those treated with analgesics, 24.3% received opioids compared to 75.7% receiving opioid alternatives in the ED and at D/C, including non-pharmacological modalities. Demographics showed among patients receiving analgesics, 56.7% were aged between 18-64, 51.8% were male, 51.7% were white, and 66.2% had government funded health insurance. Ninety-one percent of all opioids prescribed were in the ED, with intravenous (IV) morphine, IV fentanyl, and morphine sulfate immediate release (MSIR) tablets accounting for 88.0% of ED dispensed opioids. With 9.3% of all opioids prescribed at D/C, MSIR was dispensed 72.1% of the time. Hydrocodone, oxycodone, and tramadol usage to only 10-15% of the time, and hydromorphone at 0%. Of opioid alternatives, non-steroidal anti-inflammatory drugs were utilized 60.3% of the time, 23.5% with local anesthetics and ultrasound-guided nerve blocks, and 7.9% with acetaminophen as the primary non-opioid drug categories prescribed by ED providers. Non-pharmacological analgesia included virtual reality and other modalities. An average of 18.5 ED opioid orders and 1.9 opioid D/C prescriptions per 102.4 daily ED patient visits was observed for the period. Compared to other specialties within our institution, 2.0% of opioid D/C prescriptions are given by ED providers, compared to the national average of 4.8%. Opioid alternatives accounted for 69.7% and 30.3% usage, versus 90.7% and 9.3% for opioids in the ED and D/C, respectively.There is a pressing need for concise, relevant, and reliable clinical data on analgesic utilization for ED providers and leadership to evaluate prescribing practices and make data-driven decisions. Basic computer software can be used to create effective visual reporting dashboards with indicators that convey relevant and timely information in an easy-to-digest manner. We accurately examined our ED's analgesic prescribing practices using CI through dashboard reporting. Such reporting tools can quickly identify key performance indicators and prioritize data to enhance pain management and promote safe prescribing practices in the emergency setting.Keywords: clinical informatics, dashboards, emergency department, health informatics, healthcare informatics, medical informatics, opioids, pain management, technology
Procedia PDF Downloads 13718 The Safe Introduction of Tocilizumab for the Treatment of SARS-CoV-2 Pneumonia at an East London District General Hospital
Authors: Andrew Read, Alice Parry, Kate Woods
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Since the advent of the SARS-CoV-2 pandemic, the search for medications that can reduce mortality and morbidity has been a global research priority. Several multi-center trials have recently demonstrated improved mortality associated with the use of Tocilizumab, an interleukin-6 receptor antagonist, in patients with severe SARS-CoV-2 pneumonia. Initial data supported the administration in patients requiring respiratory support (non-invasive or invasive ventilation), but more recent data has shown benefit in all hypoxic patients. At the height of the second wave of COVID-19 infections in London, our hospital introduced the use of Tocilizumab for patients with severe COVID-19. Tocilizumab is licensed for use in chronic inflammatory conditions and has been associated with an increased risk of severe bacterial and fungal infections, as well as reactivation of chronic viral infections (e.g., hepatitis B). It is a specialist drug that suppresses the formation of C-reactive protein (CRP) for 6 – 12 weeks. It is not widely used by the general medical community. We aimed to assess Tocilizumab use in our hospital and to implement changes to the protocol as required to ensure administration was safe and appropriate. A retrospective study design was used to assess prescriptions over an initial 3-week period in both intensive care and on the medical wards. This amounted to a total of 13 patients. The initial data collection identified four key areas of concern: adherence to national and local inclusion & exclusion criteria; a collection of appropriate screening blood prior to administration; documentation of informed consent or best interest decision and documentation of Tocilizumab administration on patient discharge information, to alert future healthcare providers that typical measures of inflammation and infection, such as CRP, are unreliable for up to 3-months. Data were collected from electronic notes, blood results and observation charts, and cross referenced with pharmacy data. Initial results showed that all four key areas were completed in approximately 50% of cases. Of particular concern was adherence to exclusion criteria, such as current evidence of bacterial infection, and ensuring the correct screening blood was sent to exclude infections such as hepatitis. To remedy this and improve patient safety, the initial data was presented to relevant healthcare professionals. Subsequently, three interventions were introduced and education on each provided to hospital staff. An electronic ‘order set’ collating the appropriate screening blood was created simplifying the screening process. Pre-formed electronic documentation which can be inserted into the notes was created to provide a framework for consent discussions and reduce the time needed for junior doctors to complete this task. Additionally, a ‘Tocilizumab’ administration card was created and administered via pharmacy. This was distributed to each patient on discharge to ensure future healthcare professionals were aware of the potential effects of Tocilizumab administration, including suppression of CRP. Following these changes, repeat data collection over two months illustrated that each of the 4 safety aspects was met with a 100% success rate in every patient. Although this demonstrates good progress and effective interventions the challenge will be to maintain this progress. The audit data collection is ongoingKeywords: education, patient safety , SARS-CoV-2, Tocilizumab
Procedia PDF Downloads 17217 India’s Neighborhood Policy and the Northeast: Exploratory Study of the Nagas in the Indo-Myanmar Border
Authors: Sachoiba Inkah
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The Northeast region has not been a major factor in India’s foreign policy calculation since independence. Instead, the region was ignored and marginalized even to the extent of using force and repressive Acts such as AFSPA(Armed Forces Special Powers Act) to suppress the voices of both states and non-state actors. The liberalization of the economy in the 90s in the wake of globalization gave India a new outlook and the Look East Policy (LEP) was a paradigm shift in India’s engagement with the Southeast Asian nations as it seeks to explore the benefits of the ASEAN. The reorienting of India’s foreign policy to ‘Neighborhood First” is attributed to the present political dispensation, which is further widened to include ‘Extended Neighborhood.’ As a result, the Northeastern states have become key players in India’s participation in regional groupings such as SAARC, BIMSTEC, and BCIM. The need for external balancing, diplomacy and development has reset India’s foreign policy priorities as the Northeast states lie in the confluence of South Asia, Southeast and East Asia, and a stakeholder in Act East Policy. The paper will explore the role of Northeastern states in the framework of Indian foreign policy as it shares international boundaries with China, Bhutan, Bangladesh, and Myanmar and most importantly, study the case of Nagas who are spread across Manipur, Nagaland, and Arunachal Pradesh bordering Myanmar. The Indo-Myanmar border is an area of conflict and various illegal activities such as arms trafficking, illegal migrants, drug, and human trafficking are still being carried out and in order to address this issue, both India and Myanmar need to take into consideration the various communities living across the border. And conflict and insurgency should not be a yardstick to curtailed development of infrastructures such as roads, health facilities, transport, and communication in the contested region. The realities, perceptions, and contentions of the Northeastern states and the different communities living in the border areas need a wider discourse as the region the potential to drive India’s diplomatic relations with its neighbors and extended neighborhood. The methods employed are analytical and more of a descriptive analysis on India’s foreign policy framework with a focus on Nagas in Myanmar, drawing from both primary and secondary sources. Primary sources include official documents, data, and statistics released by various governmental agencies, parliamentary debates, political speeches, press releases, treaties and agreements, historical biographies and organizational policy papers, protocols and procedures of government conferences, regional organization study reports etc. The paper concludes that the recent proactive engagement between India and Myanmar on trade, defense, economic, and infrastructure development are positive signs cementing bilateral ties, but there is not much room for the people-to-people connect, especially for people living in the borderland. The Freedom of Movement Regime that is in place is limited and there is more scope for improvement as people in the borderland looks towards trade and commerce to not only uplift the border economy but also act as a catalyst for robust engagement between the two countries, albeit with more infrastructure such as road, healthcare, education, a tourist hotspot, trade centers, mobile connectivity, etc.Keywords: foreign policy, infrastructure development, insurgency, people to people connect
Procedia PDF Downloads 19016 A Case of Severe Iatrogenic Cushing’s Syndrome Followed by Adrenal Crisis, Multifocal Pneumonia, Sepsis, Pulmonary Embolism and Prolonged Adrenal Insufficiency
Authors: Jelena Maletkovic
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Background: Endogenous Cushing’s syndrome is a rare disease, but iatrogenic or drug related Cushing syndrome from glucocorticoid products is commonly seen in clinical practice. With high dose and long term use of glucocorticoids, patients can develop isolated hypothalamic-pituitary-adrenal (HPA) suppression, or HPA axis suppression can be accompanied by overt iatrogenic Cushing’s syndrome. This is a rare case where severe Cushing’s syndrome developed from an unknown medication and was followed by severe and prolonged adrenal insufficiency and multiple potentially fatal complications. Case: This is a 37-year-old woman who is presented to Emergency Room (ER) with shortness of breath and chest pain. Four months prior to this presentation the patient was a generally healthy woman who was looking for improvement in her appearance and visited local Rejuvenation Clinic. After initial consultation with a nurse, she was contacted by a physician over the phone and was advised to start taking multiple injectable medications that will arrive by mail. Medications without any labels on bottles were delivered and the patient started daily intramuscular injections. Over the next two months, she noticed rounding of her face and swelling around her eyes. She gained 20 pounds, mostly abdominal fat and became extremely fatigued. Her muscles on legs were visibly decreasing in size and she felt significant muscle weakness. Unexplained bruising occurred. She started growing hair on face and developed secondary amenorrhea. New severe back pain started. She developed depression and headaches. Finally, over a few days, a number of red-purple stretch marks that were sensitive and painful appeared over her abdomen, upper part of arms and legs. She then became suspicious that these dramatic symptoms are caused by injectable medication and she discontinued injections. Over the next few days she presented to ER with low blood pressure and oxygen saturation of 75%. Studies revealed extensive pneumonia as well as multiple pulmonary emboli. Her white blood count was elevated with 32 000 and she also had acute kidney failure on admission. She was treated for sepsis and was also given stress dose steroids. Steroids were tapered over 48 hours and discontinued. After being discharged to home, on her first visit to endocrinology clinic she had undetectable ACTH of < 2pg/mL and undetectable 8am cortisol of < 0.2mcg/dL. She did not respond to an intramuscular injection of cosyntropin 250mcg and her repeated cortisol after 60 minutes was only 1mcg/dL. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone 20mg+10mg. It took close to 2 years of slow tapering for recovery of this patient’s HPA axis and resolve all the sequelae from Cushing’s syndrome. Conclusion: Misuse and abuse of glucocorticoids have been present almost since these medications were discovered. This is a rare case where not only severe Cushing’s syndrome in full clinical picture developed but also the patient suffered multiple potentially fatal complications and prolonged adrenal insufficiency. Visits to herbal, rejuvenation, esthetic, and similar clinics are becoming more and more popular and physicians need to be aware of possible non-benign nature of medications that their patients may be using.Keywords: iatrogenic, Cushing's syndrome, adrenal crisis, steroid abuse
Procedia PDF Downloads 16315 Colloid-Based Biodetection at Aqueous Electrical Interfaces Using Fluidic Dielectrophoresis
Authors: Francesca Crivellari, Nicholas Mavrogiannis, Zachary Gagnon
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Portable diagnostic methods have become increasingly important for a number of different purposes: point-of-care screening in developing nations, environmental contamination studies, bio/chemical warfare agent detection, and end-user use for commercial health monitoring. The cheapest and most portable methods currently available are paper-based – lateral flow and dipstick methods are widely available in drug stores for use in pregnancy detection and blood glucose monitoring. These tests are successful because they are cheap to produce, easy to use, and require minimally invasive sampling. While adequate for their intended uses, in the realm of blood-borne pathogens and numerous cancers, these paper-based methods become unreliable, as they lack the nM/pM sensitivity currently achieved by clinical diagnostic methods. Clinical diagnostics, however, utilize techniques involving surface plasmon resonance (SPR) and enzyme-linked immunosorbent assays (ELISAs), which are expensive and unfeasible in terms of portability. To develop a better, competitive biosensor, we must reduce the cost of one, or increase the sensitivity of the other. Electric fields are commonly utilized in microfluidic devices to manipulate particles, biomolecules, and cells. Applications in this area, however, are primarily limited to interfaces formed between immiscible interfaces. Miscible, liquid-liquid interfaces are common in microfluidic devices, and are easily reproduced with simple geometries. Here, we demonstrate the use of electrical fields at liquid-liquid electrical interfaces, known as fluidic dielectrophoresis, (fDEP) for biodetection in a microfluidic device. In this work, we apply an AC electric field across concurrent laminar streams with differing conductivities and permittivities to polarize the interface and induce a discernible, near-immediate, frequency-dependent interfacial tilt. We design this aqueous electrical interface, which becomes the biosensing “substrate,” to be intelligent – it “moves” only when a target of interest is present. This motion requires neither labels nor expensive electrical equipment, so the biosensor is inexpensive and portable, yet still capable of sensitive detection. Nanoparticles, due to their high surface-area-to-volume ratio, are often incorporated to enhance detection capabilities of schemes like SPR and fluorimetric assays. Most studies currently investigate binding at an immobilized solid-liquid or solid-gas interface, where particles are adsorbed onto a planar surface, functionalized with a receptor to create a reactive substrate, and subsequently flushed with a fluid or gas with the relevant analyte. These typically involve many preparation and rinsing steps, and are susceptible to surface fouling. Our microfluidic device is continuously flowing and renewing the “substrate,” and is thus not subject to fouling. In this work, we demonstrate the ability to electrokinetically detect biomolecules binding to functionalized nanoparticles at liquid-liquid interfaces using fDEP. In biotin-streptavidin experiments, we report binding detection limits on the order of 1-10 pM, without amplifying signals or concentrating samples. We also demonstrate the ability to detect this interfacial motion, and thus the presence of binding, using impedance spectroscopy, allowing this scheme to become non-optical, in addition to being label-free.Keywords: biodetection, dielectrophoresis, microfluidics, nanoparticles
Procedia PDF Downloads 38214 Pathophysiological Implications in Immersion Treatment Methods of Icthyophthiriasis Disease in African Catfish (Clarias gariepinus) Using Moringa oleifera Extract
Authors: Ikele Chika Bright, Mgbenka Bernard Obialo, Ikele Chioma Faith
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Icthyophthiriasis is a prevalent protozoan (ectoparasite) mostly affecting cultured and aquarium fishes. The majority of the chemotherapeutants lack efficacy for completely eliminating Ich parasite without affecting the environment and they are not safe for human health. The present work is focused on the evaluating different immersion treatments of African catfish (Clarias gariepinus) infected with ichthyophthiriasis and treated with a non-chemical and environmental friendly parasiticides Moringa oleifera. A total number of 800 apparently healthy parasites free (examined) post juvenile catfish were obtained from a reputable farm, disinfected with potassium permanganate in a quarantine tank to remove any possible external parasites. The fish were further challenged with approximately 44,000 infective stages of theronts which were obtained through serial passages by cohabitation. Seven groups (A-G) of post Juvenile were used for the experiment which was carried out into three stages; Dips (60minutes), short term treatment (24-96h) and prolong bath treatment (0-15 days). The concentrations selected were dependent on the outcome of the LC50 of the plant material from which dose-dependent factors were used to select various concentrations of the treatment. In Dips treatment, group D-G were treated with 1,500mg/L, 2500mg/L., 3500mg/L and 4500mg/L, short-term treatment was treated with 150mg/L, 250mg/L, 350mg/L and 450mg/L and prolong bath was treated with 15mg/L, 25mg/L, 35mg/L and 45mg/L of the plant extract whereas group A, B and C were normal control, Ich- infested not treated and Ich- infested treated with standard drug (Acriflavin), respectively. The various types of treatment applied with corresponding concentrations showed almost complete elimination of the adult parasites (trophonts) both in the gills and the body smear, thereby making M. oleifera a potential parasiticides. There were serious pathological alterations in the skin and gills which are usually the main point for Ich parasites invasion but no significant morphological characteristics was noted among the treated groups subjected to different immersion treatment patterns. Epitheliocystis, aneurysm, oedema, hemorrhage, and localization of the adult parasite in the gills were the overall common observations made in the gills whereas degeneration of muscle fibre, dermatitis, hemorrhage, oedema, abscess formation and keratinisation were observed in the skin. However, there are no pathological changes in the control group. Moreover, biochemical parameters such as urea, creatinine, albumin., globulin, total protein, ALT, AST), blood chemistry (sodium, chloride, potassium, bicarbonate), antioxidants (CAT, SOD, GPx, LPO), enzymatic activities (myeloperoxidase, thioreadoxin reductase), Inflammatory response (C-reactive protein), Stress markers (lactate dehydrogenase), heamatological parameters (RBC, PCV, WBC, HB and differential count), lipid profile (total cholesterol, tryglycerides , high density lipoprotein and low density lipoprotein) all showed various significant (P<0.05) and no significant (P>0.05) responses among the Ich-infested fish treated under three immersion treatments. It is suggested that M. oleifera may serve as an alternatives to chemotherapeutants for control of Ichthyophthiriasis in African catfish Clarias gariepinus.Keywords: Icthyophthirius multifilis, immersion treatment, pathophysiology, African catfish
Procedia PDF Downloads 38113 Psoriasis Diagnostic Test Development: Exploratory Study
Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein
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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy
Procedia PDF Downloads 10912 A Quantitative Case Study Analysis of Store Format Contributors to U.S. County Obesity Prevalence in Virginia
Authors: Bailey Houghtaling, Sarah Misyak
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Food access; the availability, affordability, convenience, and desirability of food and beverage products within communities, is influential on consumers’ purchasing and consumption decisions. These variables may contribute to lower dietary quality scores and a higher obesity prevalence documented among rural and disadvantaged populations in the United States (U.S.). Current research assessing linkages between food access and obesity outcomes has primarily focused on distance to a traditional grocery/supermarket store as a measure of optimality. However, low-income consumers especially, including U.S. Department of Agriculture’s Supplemental Nutrition Assistance Program (SNAP) participants, seem to utilize non-traditional food store formats with greater frequency for household dietary needs. Non-traditional formats have been associated with less nutritious food and beverage options and consumer purchases that are high in saturated fats, added sugars, and sodium. Authors’ formative research indicated differences by U.S. region and rurality in the distribution of traditional and non-traditional SNAP-authorized food store formats. Therefore, using Virginia as a case study, the purpose of this research was to determine if a relationship between store format, rurality, and obesity exists. This research applied SNAP-authorized food store data (food access points for SNAP as well as non-SNAP consumers) and obesity prevalence data by Virginia county using publicly available databases: (1) SNAP Retailer Locator, and; (2) U.S. County Health Rankings. The alpha level was set a priori at 0.05. All Virginia SNAP-authorized stores (n=6,461) were coded by format – grocery, drug, mass merchandiser, club, convenience, dollar, supercenter, specialty, farmers market, independent grocer, and non-food store. Simple linear regression was applied primarily to assess the relationship between store format and obesity. Thereafter, multiple variables were added to the regression to account for potential moderating relationships (e.g., county income, rurality). Convenience, dollar, non-food or restaurant, mass merchandiser, farmers market, and independent grocer formats were significantly, positively related to obesity prevalence. Upon controlling for urban-rural status and income, results indicated the following formats to be significantly related to county obesity prevalence with a small, positive effect: convenience (p=0.010), accounting for 0.3% of the variance in obesity prevalence; dollar (p=0.005; 0.5% of the variance), and; non-food (p=0.030; 1.3% of the variance) formats. These results align with current literature on consumer behavior at non-traditional formats. For example, consumers’ food and beverage purchases at convenience and dollar stores are documented to be high in saturated fats, added sugars, and sodium. Further, non-food stores (i.e., quick-serve restaurants) often contribute to a large portion of U.S. consumers’ dietary intake and thus poor dietary quality scores. Current food access research investigates grocery/supermarket access and obesity outcomes. These results suggest more research is needed that focuses on non-traditional food store formats. Nutrition interventions within convenience, dollar, and non-food stores, for example, that aim to enhance not only healthy food access but the affordability, convenience, and desirability of nutritious food and beverage options may impact obesity rates in Virginia. More research is warranted utilizing the presented investigative framework in other U.S. and global regions to explore the role and the potential of non-traditional food store formats to prevent and reduce obesity.Keywords: food access, food store format, non-traditional food stores, obesity prevalence
Procedia PDF Downloads 13111 Bioinspired Green Synthesis of Magnetite Nanoparticles Using Room-Temperature Co-Precipitation: A Study of the Effect of Amine Additives on Particle Morphology in Fluidic Systems
Authors: Laura Norfolk, Georgina Zimbitas, Jan Sefcik, Sarah Staniland
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Magnetite nanoparticles (MNP) have been an area of increasing research interest due to their extensive applications in industry, such as in carbon capture, water purification, and crucially, the biomedical industry. The use of MNP in the biomedical industry is rising, with studies on their effect as Magnetic resonance imaging contrast agents, drug delivery systems, and as hyperthermic cancer treatments becoming prevalent in the nanomaterial research community. Particles used for biomedical purposes must meet stringent criteria; the particles must have consistent shape and size between particles. Variation between particle morphology can drastically alter the effective surface area of the material, making it difficult to correctly dose particles that are not homogeneous. Particles of defined shape such as octahedral and cubic have been shown to outperform irregular shaped particles in some applications, leading to the need to synthesize particles of defined shape. In nature, highly homogeneous MNP are found within magnetotactic bacteria, a unique bacteria capable of producing magnetite nanoparticles internally under ambient conditions. Biomineralisation proteins control the properties of the MNPs, enhancing their homogeneity. One of these proteins, Mms6, has been successfully isolated and used in vitro as an additive in room-temperature co-precipitation reactions (RTCP) to produce particles of defined mono-dispersed size & morphology. When considering future industrial scale-up it is crucial to consider the costs and feasibility of an additive, as an additive that is not readily available or easily synthesized at a competitive price will not be sustainable. As such, additives selected for this research are inspired by the functional groups of biomineralisation proteins, but cost-effective, environmentally friendly, and compatible with scale-up. Diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA), and pentaethylenehexamine (PEHA) have been successfully used in RTCP to modulate the properties of particles synthesized, leading to the formation of octahedral nanoparticles with no use of organic solvents, heating, or toxic precursors. By extending this principle to a fluidic system, ongoing research will reveal whether the amine additives can also exert morphological control in an environment which is suited toward higher particle yield. Two fluidic systems have been employed; a peristaltic turbulent flow mixing system suitable for the rapid production of MNP, and a macrofluidic system for the synthesis of tailored nanomaterials under a laminar flow regime. The presence of the amine additives in the turbulent flow system in initial results appears to offer similar morphological control as observed under RTCP conditions, with higher proportions of octahedral particles formed. This is a proof of concept which may pave the way to green synthesis of tailored MNP on an industrial scale. Mms6 and amine additives have been used in the macrofluidic system, with Mms6 allowing magnetite to be synthesized at unfavourable ferric ratios, but no longer influencing particle size. This suggests this synthetic technique while still benefiting from the addition of additives, may not allow additives to fully influence the particles formed due to the faster timescale of reaction. The amine additives have been tested at various concentrations, the results of which will be discussed in this paper.Keywords: bioinspired, green synthesis, fluidic, magnetite, morphological control, scale-up
Procedia PDF Downloads 11110 Impact of Simulated Brain Interstitial Fluid Flow on the Chemokine CXC-Chemokine-Ligand-12 Release From an Alginate-Based Hydrogel
Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon
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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling
Procedia PDF Downloads 789 In-situ Mental Health Simulation with Airline Pilot Observation of Human Factors
Authors: Mumtaz Mooncey, Alexander Jolly, Megan Fisher, Kerry Robinson, Robert Lloyd, Dave Fielding
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Introduction: The integration of the WingFactors in-situ simulation programme has transformed the education landscape at the Whittington Health NHS Trust. To date, there have been a total of 90 simulations - 19 aimed at Paediatric trainees, including 2 Child and Adolescent Mental Health (CAMHS) scenarios. The opportunity for joint debriefs provided by clinical faculty and airline pilots, has created a new exciting avenue to explore human factors within psychiatry. Through the use of real clinical environments and primed actors; the benefits of high fidelity simulation, interdisciplinary and interprofessional learning has been highlighted. The use of in-situ simulation within Psychiatry is a newly emerging concept and its success here has been recognised by unanimously positive feedback from participants and acknowledgement through nomination for the Health Service Journal (HSJ) Award (Best Education Programme 2021). Methodology: The first CAMHS simulation featured a collapsed patient in the toilet with a ligature tied around her neck, accompanied by a distressed parent. This required participants to consider:; emergency physical management of the case, alongside helping to contain the mother and maintaining situational awareness when transferring the patient to an appropriate clinical area. The second simulation was based on a 17- year- old girl attempting to leave the ward after presenting with an overdose, posing potential risk to herself. The safe learning environment enabled participants to explore techniques to engage the young person and understand their concerns, and consider the involvement of other members of the multidisciplinary team. The scenarios were followed by an immediate ‘hot’ debrief, combining technical feedback with Human Factors feedback from uniformed airline pilots and clinicians. The importance of psychological safety was paramount, encouraging open and honest contributions from all participants. Key learning points were summarized into written documents and circulated. Findings: The in-situ simulations demonstrated the need for practical changes both in the Emergency Department and on the Paediatric ward. The presence of airline pilots provided a novel way to debrief on Human Factors. The following key themes were identified: -Team-briefing (‘Golden 5 minutes’) - Taking a few moments to establish experience, initial roles and strategies amongst the team can reduce the need for conversations in front of a distressed patient or anxious relative. -Use of checklists / guidelines - Principles associated with checklist usage (control of pace, rigor, team situational awareness), instead of reliance on accurate memory recall when under pressure. -Read-back - Immediate repetition of safety critical instructions (e.g. drug / dosage) to mitigate the risks associated with miscommunication. -Distraction management - Balancing the risk of losing a team member to manage a distressed relative, versus it impacting on the care of the young person. -Task allocation - The value of the implementation of ‘The 5A’s’ (Availability, Address, Allocate, Ask, Advise), for effective task allocation. Conclusion: 100% of participants have requested more simulation training. Involvement of airline pilots has led to a shift in hospital culture, bringing to the forefront the value of Human Factors focused training and multidisciplinary simulation. This has been of significant value in not only physical health, but also mental health simulation.Keywords: human factors, in-situ simulation, inter-professional, multidisciplinary
Procedia PDF Downloads 1048 Cardiolipin-Incorporated Liposomes Carrying Curcumin and Nerve Growth Factor to Rescue Neurons from Apoptosis for Alzheimer’s Disease Treatment
Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou
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Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase
Procedia PDF Downloads 3287 Suicidal Attempts as a Reason for Emergency Medical Teams’ Call-Outs Based on Examples of Ambulance Service in Siedlce, Poland
Authors: Dawid Jakimiuk, Krzysztof Mitura, Leszek Szpakowski, Sławomir Pilip, Daniel Celiński
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The Emergency Medical Teams (EMS) of the Ambulance Service in Siedlce serve the population living in the Mazowieckie Voivodeship (the area of eastern Poland with approximately 550,000 inhabitants). They provide health services at the pre-hospital stage to all life-threatening patients. The analysis covered the interventions of emergency medical teams in cases of suicide attempts that occurred in the years 2015-2018. The study was retrospective. The data was obtained on the basis of digital medical records of completed call-outs. When defining the disease entity, the International Statistical Classification of Diseases and Health Problems ICD-10 prepared by WHO was used. The relationship between selected disease entities and the area of EMT intervention, the patient's sex and age, and the time of occurrence of the event were investigated. Non-urban area was defined as the area inhabited by a population below 10,000 residents. Statistical analysis was performed using Pearson's Chi ^ 2 test and presenting the percentage of cases in the study group. Of all the suicide attempts, drug abuse cases were the most frequent, including: X60 (Intentional self-poisoning by and exposure to nonopioid analgesics, antipyretics and antirheumatics); X61 (Intentional self-poisoning by and exposure to antiepileptic, sedative-hypnotic, antiparkinsonian and psychotropic drugs, not elsewhere classified); X62 (Intentional self-poisoning by and exposure to narcotics and psycholeptics [hallucinogens], not elsewhere classified); X63 (Intentional self-poisoning by and exposure to other drugs acting on the autonomic nervous system); X64 (Intentional self-poisoning by and exposure to other and unspecified drugs, medicaments and biological substance) oraz X70 (Intentional self-harm by hanging, strangulation and suffocation). In total, they accounted for 69.4% of all interventions to suicide attempts in the studied period. Statistical analysis shows significant differences (χ2 = 39.30239, p <0.0001, n = 561) between the area of EMT intervention and the type of suicide attempt. In non-urban areas, a higher percentage of X70 diagnoses was recorded (55.67%), while in urban areas, X60-X64 (72.53%). In non-urban areas, a higher proportion of patients attempting suicide was observed compared to patients living in urban areas. For X70 and X60 - X64 in total, the incidence rates in non-urban areas were 80.8% and 56%, respectively. Significant differences were found (χ2 = 119.3304, p <0.0001, n = 561) depending on the method of attempting suicide in relation to the patient's sex. The percentage of women diagnosed with X60-X64 versus X70 was 87.50%, which was the largest number of patients (n = 154) as compared to men. In the case of X70 in relation to X60-X64, the percentage of men was 62.08%, which was the largest number of patients (n = 239) as compared to women (n = 22). In the case of X70, the percentage of men compared to women was as high as 92%. Significant differences were observed (χ2 = 14.94848, p <0.01058) between the hour of EMT intervention and the type of suicide attempt. The highest percentage of X70 occurred between 04:01 - 08:00 (64.44%), while X60-X64 between 00:01 - 04:00 (70.45%). The largest number of cases of all tested suicide attempts was recorded between 16:01 - 20:00 for X70 (n = 62), X60 - X64 (n = 82), respectively. The highest percentage of patients undertaking all suicide attempts studied at work was observed in the age range of 18-30 (31.5%), while the lowest was in the age group over 60 years of age. (11%). There was no significant correlation between the day of the week or individual months of the year and the type of suicide attempt - respectively (χ2 = 6.281729, p <0.39238, n = 561) and (χ2 = 3.348913, p <0.9857, n = 561). There were also no significant differences in the incidence of suicide attempts for each year in the study period (χ2 = 3.348913, p <0.9857 n = 561). The obtained results suggest the necessity to undertake preventive measures in order to minimize the number of suicide attempts. Such activities should be directed especially at young patients living in non-urban areas.Keywords: emergency med, emergency medical team, attempted suicide, pre-hospital
Procedia PDF Downloads 896 Effect of Degree of Phosphorylation on Electrospinning and In vitro Cell Behavior of Phosphorylated Polymers as Biomimetic Materials for Tissue Engineering Applications
Authors: Pallab Datta, Jyotirmoy Chatterjee, Santanu Dhara
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Over the past few years, phosphorous containing polymers have received widespread attention for applications such as high performance optical fibers, flame retardant materials, drug delivery and tissue engineering. Being pentavalent, phosphorous can exist in different chemical environments in these polymers which increase their versatility. In human biochemistry, phosphorous based compounds exert their functions both in soluble and insoluble form occurring as inorganic or as organophosphorous compounds. Specifically in case of biomacromolecules, phosphates are critical for functions of DNA, ATP, phosphoproteins, phospholipids, phosphoglycans and several coenzymes. Inspired by the role of phosphorous in functional biomacromolecules, design and synthesis of biomimetic materials are thus carried out by several authors to study macromolecular function or as substitutes in clinical tissue regeneration conditions. In addition, many regulatory signals of the body are controlled by phoshphorylation of key proteins present either in form of growth factors or matrix-bound scaffold proteins. This inspires works on synthesis of phospho-peptidomimetic amino acids for understanding key signaling pathways and this is extended to obtain molecules with potentially useful biological properties. Apart from above applications, phosphate groups bound to polymer backbones have also been demonstrated to improve function of osteoblast cells and augment performance of bone grafts. Despite the advantages of phosphate grafting, however, there is limited understanding on effect of degree of phosphorylation on macromolecular physicochemical and/or biological properties. Such investigations are necessary to effectively translate knowledge of macromolecular biochemistry into relevant clinical products since they directly influence processability of these polymers into suitable scaffold structures and control subsequent biological response. Amongst various techniques for fabrication of biomimetic scaffolds, nanofibrous scaffolds fabricated by electrospinning technique offer some special advantages in resembling the attributes of natural extracellular matrix. Understanding changes in physico-chemical properties of polymers as function of phosphorylation is therefore going to be crucial in development of nanofiber scaffolds based on phosphorylated polymers. The aim of the present work is to investigate the effect of phosphorous grafting on the electrospinning behavior of polymers with aim to obtain biomaterials for bone regeneration applications. For this purpose, phosphorylated derivatives of two polymers of widely different electrospinning behaviors were selected as starting materials. Poly(vinyl alcohol) is a conveniently electrospinnable polymer at different conditions and concentrations. On the other hand, electrospinning of chitosan backbone based polymers have been viewed as a critical challenge. The phosphorylated derivatives of these polymers were synthesized, characterized and electrospinning behavior of various solutions containing these derivatives was compared with electrospinning of pure poly (vinyl alcohol). In PVA, phosphorylation adversely impacted electrospinnability while in NMPC, higher phosphate content widened concentration range for nanofiber formation. Culture of MG-63 cells on electrospun nanofibers, revealed that degree of phosphate modification of a polymer significantly improves cell adhesion or osteoblast function of cultured cells. It is concluded that improvement of cell response parameters of nanofiber scaffolds can be attained as a function of controlled degree of phosphate grafting in polymeric biomaterials with implications for bone tissue engineering applications.Keywords: bone regeneration, chitosan, electrospinning, phosphorylation
Procedia PDF Downloads 2165 Establishment of a Classifier Model for Early Prediction of Acute Delirium in Adult Intensive Care Unit Using Machine Learning
Authors: Pei Yi Lin
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Objective: The objective of this study is to use machine learning methods to build an early prediction classifier model for acute delirium to improve the quality of medical care for intensive care patients. Background: Delirium is a common acute and sudden disturbance of consciousness in critically ill patients. After the occurrence, it is easy to prolong the length of hospital stay and increase medical costs and mortality. In 2021, the incidence of delirium in the intensive care unit of internal medicine was as high as 59.78%, which indirectly prolonged the average length of hospital stay by 8.28 days, and the mortality rate is about 2.22% in the past three years. Therefore, it is expected to build a delirium prediction classifier through big data analysis and machine learning methods to detect delirium early. Method: This study is a retrospective study, using the artificial intelligence big data database to extract the characteristic factors related to delirium in intensive care unit patients and let the machine learn. The study included patients aged over 20 years old who were admitted to the intensive care unit between May 1, 2022, and December 31, 2022, excluding GCS assessment <4 points, admission to ICU for less than 24 hours, and CAM-ICU evaluation. The CAMICU delirium assessment results every 8 hours within 30 days of hospitalization are regarded as an event, and the cumulative data from ICU admission to the prediction time point are extracted to predict the possibility of delirium occurring in the next 8 hours, and collect a total of 63,754 research case data, extract 12 feature selections to train the model, including age, sex, average ICU stay hours, visual and auditory abnormalities, RASS assessment score, APACHE-II Score score, number of invasive catheters indwelling, restraint and sedative and hypnotic drugs. Through feature data cleaning, processing and KNN interpolation method supplementation, a total of 54595 research case events were extracted to provide machine learning model analysis, using the research events from May 01 to November 30, 2022, as the model training data, 80% of which is the training set for model training, and 20% for the internal verification of the verification set, and then from December 01 to December 2022 The CU research event on the 31st is an external verification set data, and finally the model inference and performance evaluation are performed, and then the model has trained again by adjusting the model parameters. Results: In this study, XG Boost, Random Forest, Logistic Regression, and Decision Tree were used to analyze and compare four machine learning models. The average accuracy rate of internal verification was highest in Random Forest (AUC=0.86), and the average accuracy rate of external verification was in Random Forest and XG Boost was the highest, AUC was 0.86, and the average accuracy of cross-validation was the highest in Random Forest (ACC=0.77). Conclusion: Clinically, medical staff usually conduct CAM-ICU assessments at the bedside of critically ill patients in clinical practice, but there is a lack of machine learning classification methods to assist ICU patients in real-time assessment, resulting in the inability to provide more objective and continuous monitoring data to assist Clinical staff can more accurately identify and predict the occurrence of delirium in patients. It is hoped that the development and construction of predictive models through machine learning can predict delirium early and immediately, make clinical decisions at the best time, and cooperate with PADIS delirium care measures to provide individualized non-drug interventional care measures to maintain patient safety, and then Improve the quality of care.Keywords: critically ill patients, machine learning methods, delirium prediction, classifier model
Procedia PDF Downloads 634 White-Rot Fungi Phellinus as a Source of Antioxidant and Antitumor Agents
Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair
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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae
Procedia PDF Downloads 2953 Amino Acid Based Biodegradable Poly (Ester-Amide)s and Their Potential Biomedical Applications as Drug Delivery Containers and Antibacterial
Authors: Nino Kupatadze, Tamar Memanishvili, Natia Ochkhikidze, David Tugushi, Zaal Kokaia, Ramaz Katsarava
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Amino acid-based Biodegradable poly(ester-amide)s (PEAs) have gained considerable interest as a promising materials for numerous biomedical applications. These polymers reveal a high biocompatibility and easily form small particles suitable for delivery various biological, as well as elastic bio-erodible films serving as matrices for constructing antibacterial coatings. In the present work we have demonstrated a potential of the PEAs for two applications: 1. cell therapy for stroke as vehicles for delivery and sustained release of growth factors, 2. bactericidal coating as prevention biofilm and applicable in infected wound management. Stroke remains the main cause of adult disability with limited treatment options. Although stem cell therapy is a promising strategy, it still requires improvement of cell survival, differentiation and tissue modulation. .Recently, microspheres (MPs) made of biodegradable polymers have gained significant attention for providing necessary support of transplanted cells. To investigate this strategy in the cell therapy of stroke, MPs loaded with transcription factors Wnt3A/BMP4 were prepared. These proteins have been shown to mediate the maturation of the cortical neurons. We have suggested that implantation of these materials could create a suitable microenvironment for implanted cells. Particles with spherical shape, porous surface, and 5-40 m in size (monitored by scanning electron microscopy) were made on the basis of the original PEA composed of adipic acid, L-phenylalanine and 1,4-butanediol. After 4 months transplantation of MPs in rodent brain, no inflammation was observed. Additionally, factors were successfully released from MPs and affected neuronal cell differentiation in in vitro. The in vivo study using loaded MPs is in progress. Another severe problem in biomedicine is prevention of surgical devices from biofilm formation. Antimicrobial polymeric coatings are most effective “shields” to protect surfaces/devices from biofilm formation. Among matrices for constructing the coatings preference should be given to bio-erodible polymers. Such types of coatings will play a role of “unstable seating” that will not allow bacteria to occupy the surface. In other words, bio-erodible coatings would be discomfort shelter for bacteria that along with releasing “killers of bacteria” should prevent the formation of biofilm. For this purpose, we selected an original biodegradable PEA composed of L-leucine, 1,6-hexanediol and sebacic acid as a bio-erodible matrix, and nanosilver (AgNPs) as a bactericidal agent (“killer of bacteria”). Such nanocomposite material is also promising in treatment of superficial wound and ulcer. The solubility of the PEA in ethanol allows to reduce AgNO3 to NPs directly in the solution, where the solvent served as a reductive agent, and the PEA served as NPs stabilizer. The photochemical reduction was selected as a basic method to form NPs. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscope (TEM), and dynamic light scattering (DLS). According to the UV-data and TEM data the photochemical reduction resulted in spherical AgNPs with wide particle size distribution with a high contribution of the particles below 10 nm that are known as responsible for bactericidal activity of AgNPs. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within ca. 50 nm.Keywords: biodegradable polymers, microparticles, nanocomposites, stem cell therapy, stroke
Procedia PDF Downloads 3912 Femicide: The Political and Social Blind Spot in the Legal and Welfare State of Germany
Authors: Kristina F. Wolff
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Background: In the Federal Republic of Germany, violence against women is deeply embedded in society. Germany is, as of March 2020, the most populous member state of the European Union with 83.2 million inhabitants and, although more than half of its inhabitants are women, gender equality was not certified in the Basic Law until 1957. Women have only been allowed to enter paid employment without their husband's consent since 1977 and have marital rape prosecuted only since 1997. While the lack of equality between men and women is named in the preamble of the Istanbul Convention as the cause of gender-specific, structural, traditional violence against women, Germany continues to sink on the latest Gender Equality Index. According to Police Crime Statistics (PCS), women are significantly more often victims of lethal violence, emanating from men than vice versa. The PCS, which, since 2015, also collects gender-specific data on violent crimes, is kept by the Federal Criminal Police Office, but without taking into account the relevant criteria for targeted prevention, such as the history of violence of the perpetrator/killer, weapon, motivation, etc.. Institutions such as EIGE or the World Health Organization have been asking Germany for years in vain for comparable data on violence against women in order to gain an overview or to develop cross-border synergies. The PCS are the only official data collection on violence against women. All players involved are depend on this data set, which is published only in November of the following year and is thus already completely outdated at the time of publication. In order to combat German femicides causally, purposefully and efficiently, evidence-based data was urgently needed. Methodology: Beginning in January 2019, a database was set up that now tracks more than 600 German femicides, broken down by more than 100 crime-related individual criteria, which in turn go far beyond the official PCS. These data are evaluated on the one hand by daily media research, and on the other hand by case-specific inquiries at the respective public prosecutor's offices and courts nationwide. This quantitative long-term study covers domestic violence as well as a variety of different types of gender-specific, lethal violence, including, for example, femicides committed by German citizens abroad. Additionallyalcohol/ narcotic and/or drug abuse, infanticides and the gender aspect in the judiciary are also considered. Results: Since November 2020, evidence-based data from a scientific survey have been available for the first time in Germany, supplementing the rudimentary picture of reality provided by PCS with a number of relevant parameters. The most important goal of the study is to identify "red flags" that enable general preventive awareness, that serve increasingly precise hazard assessment in acute hazard situations, and from which concrete instructions for action can be identified. Already at a very early stage of the study it could be proven that in more than half of all femicides with a sexual perpetrator/victim constellation there was an age difference of five years or more. Summary: Without reliable data and an understanding of the nature and extent, cause and effect, it is impossible to sustainably curb violence against girls and women, which increasingly often culminates in femicide. In Germany, valid data from a scientific survey has been available for the first time since November 2020, supplementing the rudimentary reality picture of the official and, to date, sole crime statistics with several relevant parameters. The basic research provides insights into geo-concentration, monthly peaks and the modus operandi of male violent excesses. A significant increase of child homicides in the course of femicides and/or child homicides as an instrument of violence against the mother could be proven as well as a danger of affected persons due to an age difference of five years and more. In view of the steadily increasing wave of violence against women, these study results are an eminent contribution to the preventive containment of German femicides.Keywords: femicide, violence against women, gender specific data, rule Of law, Istanbul convention, gender equality, gender based violence
Procedia PDF Downloads 851 Acute Severe Hyponatremia in Patient with Psychogenic Polydipsia, Learning Disability and Epilepsy
Authors: Anisa Suraya Ab Razak, Izza Hayat
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Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia
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